Erythropoietin as a Neuroprotectant for Neonatal Brain Injury: Animal Models - Tissue-Protective Cytokines: Methods and Protocols - page 109

Chapter 7

Erythropoietin as a Neuroprotectant for Neonatal Brain
Injury: Animal Models

Christopher M. Traudt and Sandra E. Juul

Abstract

Prematurity and perinatal hypoxia-ischemia are common problems that result in significant neurodevelop-
mental morbidity and high mortality worldwide. The Vannucci model of unilateral brain injury was devel-
oped to model perinatal brain injury due to hypoxia-ischemia. Because the rodent brain is altricial, i.e., it
develops postnatally, investigators can model either preterm or term brain injury by varying the age at
which injury is induced. This model has allowed investigators to better understand developmental changes
that occur in susceptibility of the brain to injury, evolution of brain injury over time, and response to
potential neuroprotective treatments. The Vannucci model combines unilateral common carotid artery
ligation with a hypoxic insult. This produces injury of the cerebral cortex, basal ganglia, hippocampus, and
periventricular white matter ipsilateral to the ligated artery. Varying degrees of injury can be obtained by
varying the depth and duration of the hypoxic insult. This chapter details one approach to the Vannucci
model and also reviews the neuroprotective effects of erythropoietin (Epo), a neuroprotective treatment
that has been extensively investigated using this model and others.

Key words Vannucci model, Erythropoietin, Hypoxic-ischemia, Common carotid artery ligation

1 Introduction

Extreme prematurity and neonatal encephalopathy significantly
impair the outcomes of affected infants. Even with optimal care,
both conditions carry a 50% risk of death, or in survivors, mental
retardation, cerebral palsy, hydrocephalus, and seizures. One of
eight babies is born preterm, with 1 in 100 born at the extreme
end of the spectrum (less than 28 weeks of gestation). Neonatal
encephalopathy occurs in 3-5 of every 1,000 live births.
Consequences of these conditions bring heartbreak for the child
and family as well as expense. Loss of productivity, dependency,
recurrent use of medical and rehabilitation services, and reduced
life expectancy all exacerbate the burden ( 1-4 ). Many factors
influence the outcomes of these vulnerable neonates, including
the duration and severity of brain injury, brain maturity at time of

1.1 Neonatal Brain

Injury